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      Iron Supplementation Influence on the Gut Microbiota and Probiotic Intake Effect in Iron Deficiency—A Literature-Based Review

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          Abstract

          Iron deficiency in the human body is a global issue with an impact on more than two billion individuals worldwide. The most important functions ensured by adequate amounts of iron in the body are related to transport and storage of oxygen, electron transfer, mediation of oxidation-reduction reactions, synthesis of hormones, the replication of DNA, cell cycle restoration and control, fixation of nitrogen, and antioxidant effects. In the case of iron deficiency, even marginal insufficiencies may impair the proper functionality of the human body. On the other hand, an excess in iron concentration has a major impact on the gut microbiota composition. There are several non-genetic causes that lead to iron deficiencies, and thus, several approaches in their treatment. The most common methods are related to food fortifications and supplements. In this review, following a summary of iron metabolism and its health implications, we analyzed the scientific literature for the influence of iron fortification and supplementation on the gut microbiome and the effect of probiotics, prebiotics, and/or synbiotics in iron absorption and availability for the organism.

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          Most cited references95

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          Bacterial iron homeostasis.

          Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators called siderophores. Ferrous iron can also be directly imported by the G protein-like transporter, FeoB. For pathogens, host-iron complexes (transferrin, lactoferrin, haem, haemoglobin) are directly used as iron sources. Bacterial iron storage proteins (ferritin, bacterioferritin) provide intracellular iron reserves for use when external supplies are restricted, and iron detoxification proteins (Dps) are employed to protect the chromosome from iron-induced free radical damage. There is evidence that bacteria control their iron requirements in response to iron availability by down-regulating the expression of iron proteins during iron-restricted growth. And finally, the expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels.
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            Probiotic bacteria reduce salmonella typhimurium intestinal colonization by competing for iron.

            Host inflammation alters the availability of nutrients such as iron to limit microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the inflamed gut by scavenging for iron with siderophores. By administering Escherichia coli strain Nissle 1917, which assimilates iron by similar mechanisms, we show that this nonpathogenic bacterium can outcompete and reduce S. Typhimurium colonization in mouse models of acute colitis and chronic persistent infection. This probiotic activity depends on E. coli Nissle iron acquisition, given that mutants deficient in iron uptake colonize the intestine but do not reduce S. Typhimurium colonization. Additionally, the ability of E. coli Nissle to overcome iron restriction by the host protein lipocalin 2, which counteracts some siderophores, is essential, given that S. Typhimurium is unaffected by E. coli Nissle in lipocalin 2-deficient mice. Thus, iron availability impacts S. Typhimurium growth, and E. coli Nissle reduces S. Typhimurium intestinal colonization by competing for this limiting nutrient. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Iron deficiency anemia: a common and curable disease.

              L. Miller (2013)
              Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                04 July 2020
                July 2020
                : 12
                : 7
                : 1993
                Affiliations
                [1 ]Department of Food Science, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania; i.oanagabrielaa@ 123456gmail.com (I.G.R.); ramona.suharoschi@ 123456usamvcluj.ro (R.S.); dan.vodnar@ 123456usamvcluj.ro (D.C.V.); carmen-rodica.pop@ 123456usamvcluj.ro (C.R.P.); sonia.socaci@ 123456usamvcluj.ro (S.A.S.); anca.farcas@ 123456usamvcluj.ro (A.C.F.); andreeadianakerezsi@ 123456gmail.com (A.D.K.); carmen.muresan@ 123456usamvcluj.ro (C.I.M.)
                [2 ]Department of Molecular Sciences, University of Medicine and Pharmacy Iuliu Hatieganu, 400349 Cluj-Napoca, Romania; romanavulturar@ 123456yahoo.co.uk
                [3 ]Cognitive Neuroscience Laboratory, University Babes-Bolyai, 400327 Cluj-Napoca, Romania
                [4 ]Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400158 Cluj-Napoca, Romania; magdaistrati@ 123456yahoo.com
                [5 ]Faculty of Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400349 Cluj-Napoca, Romania; ioana.morosan@ 123456me.com
                Author notes
                [* ]Correspondence: oana.pop@ 123456usamvcluj.ro ; Tel.: +40-748488933
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8306-8670
                https://orcid.org/0000-0001-5407-8071
                https://orcid.org/0000-0002-7798-3397
                https://orcid.org/0000-0003-0594-4628
                https://orcid.org/0000-0002-1392-4080
                https://orcid.org/0000-0003-2410-6582
                Article
                nutrients-12-01993
                10.3390/nu12071993
                7400826
                32635533
                b57af41e-ee18-4b13-90ef-80ed29ec691b
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 June 2020
                : 01 July 2020
                Categories
                Review

                Nutrition & Dietetics
                iron,diet,gut microbiota,probiotics,prebiotics
                Nutrition & Dietetics
                iron, diet, gut microbiota, probiotics, prebiotics

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